A Pilot Study to Evaluate the Safety and Efficacy of Multiple Anti-HCV Combination Therapy in Chronically Infected Hepatitis C Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 229
- 试验地点
- 3
- 主要终点
- The Proportion of Subjects Who Achieve Sustained Viral Response (SVR12) 12 Weeks After the Stop of Treatment Drugs
研究概览
简要总结
Background:
- GS-7977, GS-5885, GS-9669, and GS-9451 are new drugs for treating hepatitis C virus (HCV) infection. GS-7977 may help treat the infection when used with other treatments like interferon therapy. GS-5885, and GS-9669, and GS-9451 also lower the amount of HCV in the body. Researchers want to see whether GS-7977 can be combined with any of the other three drugs to treat HCV infection. Some participants will take GS-7977 and GS-5885. Others will take GS-7977, GS-5885 and GS-9669 or GS-7977, GS-5885 and GS-9451.
Objectives:
- To see whether GS-7977 with GS-5885 alone or in combination with either GS-9669 or 9451 can be used to treat HCV infection.
Eligibility:
Individuals at least 18 years of age who have chronic HCV infection and have never been treated for it.
Individuals at least 18 years of age who have chronic HCV infection and have not responded to interferon therapy.
Individuals at least 18 years of age who have chronic HCV infection with advanced liver disease and have never been treated for HCV
Design:
Participants will be screened with a physical exam and medical history. Blood samples will be collected. A liver biopsy may also be performed.
Some participants will take the two study drugs and some will take three study drugs. Those who take GS-7977 and GS-5885 will have one daily tablet named fixed dose combination or FDC. Those who take GS-7977 and CS-9669 will have three daily tablets taken once daily. Those who take GS-7977 and GS-5885 and GS-9451 will take 2 pills once a day. GS-7977 and GS-5885 will be combined in one pill and GS-9451 will be in another pill.
Treatment will be monitored with frequent blood tests. These tests will check liver function and the level of HCV infection. Participants may have other blood tests as needed for treatment.
Participants will have 4, 6 or 12 weeks of treatment depending on which study drugs are scheduled to take. After they complete their schedule, they will stop treatment with the study drugs. They may also have another liver biopsy.
Participants will have regular follow-up visits over the next 48 weeks. They will have physical exams and provide blood samples....
详细描述
Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated 180 million people infected worldwide. In the United States an estimated 4.1 million people are infected, and HCV is the principal cause of death from liver disease and leading indication for liver transplantation. While treatment with ribavirin (RBV) and pegylated interferon (PEG) in combination with boceprevir/telaprevir is the currently recommended therapy for chronic HCV infection and has superior cure rates compared to PEG+RBV alone in HCV monoinfected patients, treatment is still associated with a high incidence of adverse events (AEs), discontinuations, and poor cure rates in several populations. Recent studies have demonstrated that the use of a combination of antivirals, which target HCV without interferon (IFN), can cure HCV without additional toxicities. However, the determinants of response to IFN-free regimens have not been established.
This is an open label study to assess the safety, tolerability, and efficacy of treatment with GS-7977 with GS-5885, alone or in combination with GS-9669 and/or GS-9451 (selective HCV nucleotide NS5B, NS5A, nonnucleotide NS5B and NS3 inhibitors, respectively) in HCV infected treatment naive and treatment experienced patients with early and advanced liver disease. The findings from this study will aid in our understanding of determinants of response to an IFN-free regimen in HCV infected patients for both patients with early and advanced liver disease as well as in patients who are treatment naive and those who have been treated before for HCV.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
A: HCV GT-1, tx naïve, 12 wks Sofosbuvir/Ledipasvir
Oral treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885), once daily, for 12 weeks in HCV genotype 1, treatment naïve patients
干预措施: Sofosbuvir (Drug)
A: HCV GT-1, tx naïve, 12 wks Sofosbuvir/Ledipasvir
Oral treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885), once daily, for 12 weeks in HCV genotype 1, treatment naïve patients
干预措施: Ledipasvir (Drug)
B: HCV GT-1, tx naïve, 6 wks Sofosbuvir/Ledipasvir/GS-9669
Oral treatment with Sofosbuvir 400mg (GS-7977), Ledipasvir 90mg (GS-5885), GS-9669 500mg, once daily, for 6 weeks in HCV genotype 1, treatment naïve patients
干预措施: Sofosbuvir (Drug)
B: HCV GT-1, tx naïve, 6 wks Sofosbuvir/Ledipasvir/GS-9669
Oral treatment with Sofosbuvir 400mg (GS-7977), Ledipasvir 90mg (GS-5885), GS-9669 500mg, once daily, for 6 weeks in HCV genotype 1, treatment naïve patients
干预措施: Ledipasvir (Drug)
B: HCV GT-1, tx naïve, 6 wks Sofosbuvir/Ledipasvir/GS-9669
Oral treatment with Sofosbuvir 400mg (GS-7977), Ledipasvir 90mg (GS-5885), GS-9669 500mg, once daily, for 6 weeks in HCV genotype 1, treatment naïve patients
干预措施: GS-9669 (Drug)
C: HCV GT-1, tx naïve, 6 wks Sofosbuvir/Ledipasvir/GS-9451
Oral treatment with Sofosbuvir 400mg (GS-7977), Ledipasvir 90mg (GS-5885), GS-9451 80mg, once daily, for 6 weeks in HCV genotype 1, treatment naïve patients
干预措施: Sofosbuvir (Drug)
C: HCV GT-1, tx naïve, 6 wks Sofosbuvir/Ledipasvir/GS-9451
Oral treatment with Sofosbuvir 400mg (GS-7977), Ledipasvir 90mg (GS-5885), GS-9451 80mg, once daily, for 6 weeks in HCV genotype 1, treatment naïve patients
干预措施: Ledipasvir (Drug)
C: HCV GT-1, tx naïve, 6 wks Sofosbuvir/Ledipasvir/GS-9451
Oral treatment with Sofosbuvir 400mg (GS-7977), Ledipasvir 90mg (GS-5885), GS-9451 80mg, once daily, for 6 weeks in HCV genotype 1, treatment naïve patients
干预措施: GS-9451 (Drug)
D: HCV GT-1, tx-relapsed, 12 wks Sofosbuvir/Ledipasvir
Oral treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885), once daily, for 12 weeks in HCV genotype 1, treatment-relapsed patients who previously received Sofosbuvir plus Ribavirin
干预措施: Sofosbuvir (Drug)
D: HCV GT-1, tx-relapsed, 12 wks Sofosbuvir/Ledipasvir
Oral treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885), once daily, for 12 weeks in HCV genotype 1, treatment-relapsed patients who previously received Sofosbuvir plus Ribavirin
干预措施: Ledipasvir (Drug)
E: HCV GT-4, tx naïve/expd, 12 wks Sofosbuvir/Ledipasvir
Oral treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885), once daily, 12 weeks in HCV genotype 4 treatment naïve subjects and interferon treament experienced subjects
干预措施: Sofosbuvir (Drug)
E: HCV GT-4, tx naïve/expd, 12 wks Sofosbuvir/Ledipasvir
Oral treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885), once daily, 12 weeks in HCV genotype 4 treatment naïve subjects and interferon treament experienced subjects
干预措施: Ledipasvir (Drug)
F: HCV GT-1, tx naïve/expd 6 wks Sofosbuvir/Ledipasvir/GS-9451
Oral treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885) and GS-9451 80mg, once daily, 6 weeks in HCV genotype 1 treatment naïve and treatment experienced subjects with advanced liver disease
干预措施: Sofosbuvir (Drug)
F: HCV GT-1, tx naïve/expd 6 wks Sofosbuvir/Ledipasvir/GS-9451
Oral treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885) and GS-9451 80mg, once daily, 6 weeks in HCV genotype 1 treatment naïve and treatment experienced subjects with advanced liver disease
干预措施: Ledipasvir (Drug)
F: HCV GT-1, tx naïve/expd 6 wks Sofosbuvir/Ledipasvir/GS-9451
Oral treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885) and GS-9451 80mg, once daily, 6 weeks in HCV genotype 1 treatment naïve and treatment experienced subjects with advanced liver disease
干预措施: GS-9451 (Drug)
G: HCV GT-1, tx naïve, 4 wks Sofosbuvir, Ledipasvir, GS-9451
Oral Treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885) with GS-9451 80mg, once daily, 4 weeks in HCV genotype 1 treatment naïve subjects with early stage liver disease
干预措施: Sofosbuvir (Drug)
G: HCV GT-1, tx naïve, 4 wks Sofosbuvir, Ledipasvir, GS-9451
Oral Treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885) with GS-9451 80mg, once daily, 4 weeks in HCV genotype 1 treatment naïve subjects with early stage liver disease
干预措施: Ledipasvir (Drug)
G: HCV GT-1, tx naïve, 4 wks Sofosbuvir, Ledipasvir, GS-9451
Oral Treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885) with GS-9451 80mg, once daily, 4 weeks in HCV genotype 1 treatment naïve subjects with early stage liver disease
干预措施: GS-9451 (Drug)
D Retx: HCV GT-1, Re-Treatment, 12 wks Sofosbuvir, Ledipasvir
Oral treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885), once daily, 12 weeks in HCV genotype 1 subjects who failed HCV therapy in Arm B or Arm G or Arm H
干预措施: Sofosbuvir (Drug)
H: HCV GT-1, tx naïve, 4 wks Sofos/Ledip/GS-9451/GS-9669
Oral Treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885) with GS-9451 80mg, and GS-9669 250mg, once daily, 4 weeks in HCV genotype 1 treatment naïve subjects with early stage liver disease
干预措施: Sofosbuvir (Drug)
H: HCV GT-1, tx naïve, 4 wks Sofos/Ledip/GS-9451/GS-9669
Oral Treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885) with GS-9451 80mg, and GS-9669 250mg, once daily, 4 weeks in HCV genotype 1 treatment naïve subjects with early stage liver disease
干预措施: Ledipasvir (Drug)
H: HCV GT-1, tx naïve, 4 wks Sofos/Ledip/GS-9451/GS-9669
Oral Treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885) with GS-9451 80mg, and GS-9669 250mg, once daily, 4 weeks in HCV genotype 1 treatment naïve subjects with early stage liver disease
干预措施: GS-9669 (Drug)
H: HCV GT-1, tx naïve, 4 wks Sofos/Ledip/GS-9451/GS-9669
Oral Treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885) with GS-9451 80mg, and GS-9669 250mg, once daily, 4 weeks in HCV genotype 1 treatment naïve subjects with early stage liver disease
干预措施: GS-9451 (Drug)
D Retx: HCV GT-1, Re-Treatment, 12 wks Sofosbuvir, Ledipasvir
Oral treatment with Sofosbuvir 400mg (GS-7977) and Ledipasvir 90mg (GS-5885), once daily, 12 weeks in HCV genotype 1 subjects who failed HCV therapy in Arm B or Arm G or Arm H
干预措施: Ledipasvir (Drug)
结局指标
主要结局
The Proportion of Subjects Who Achieve Sustained Viral Response (SVR12) 12 Weeks After the Stop of Treatment Drugs
时间窗: 12 weeks after stop of treatment
The primary outcome was the proportion of patients with sustained viral response measured 12 weeks after the stop of treatment. The viral response was assessed by serum HCV RNA concentrations lower than 43 IU/mL - the lower limit of quantification.
次要结局
未报告次要终点